IHD causes, non lipid:

Homocysteine – oxidizes LDL

10% risk
Treatment – diet.
Lipoprotein a [Lp(a)]
15-20% of population
Increases risk
Treatment is ?
Lipoprotein a
Healthy Caucasians 20-500 g/L
Afro-Americans 50-720 g/L
Levels above 300 g/L are risk if under 55 years of
age.
95% of molecule same as plasminogen.
Lp(a) is 15% of total cholesterol so can have
normal serum cholesterol.
Lack of standards, reference methods means some
chaos in interpretation.
Gut enzyme that transports out
sterols:
Deficient then MI at age 6 – 8 years.
Plant sterols absorbed with cholesterol but
Cannot get the plant sterols out.
Atherosclerotic lesions develop from the
plant sterols
Source: Hegele at Western 2004.
Link between infection and heart
disease:
Chlamydia
Coxsackie virus
TWAR (Taiwanese acute reactin)
and others
Could heart diseases be an autoimmune disease?

Sudden unexplained death in athletes

Josef Penninger PMH.
80 year old man, chest pain and
hypotension:
Serum Cholesterol, HDL cholesterol, LDL
cholesterol and triglyceride are all normal.
Serum homocysteine increased
Serum folate decreased
Serum vitamin B12 normal
Serum vitamin B6 decreased
Cause – micronutrients deficiency?
The failing heart:
Ischaemic heart
disease
Acute coronary
syndrome
Myocardial infarction
Re infarction
Death.
Evolution of markers for
ischaemic heart disease:
ECG
Serum Cholesterol
Serum Triglyceride (fasting)
Serum HDL and LDL cholesterol, oxidized LDL
Serum Homocysteine
Serum Lp(a)
Serum C-reactive protein.
Serum troponin.
(hair loss, premature graying.)
Acute coronary insufficiency:
Pre infarct state
Serum troponins
In Europe high sensitivity serum C-reactive
protein.
Higher the level the less likely is long term
survival.
Myocardial infarction:
Chest pain: angina pectoris
ECG abnormal
Changes in plasma enzymes/proteins

Causes: atheroma, clotting. Blockage of blood

flow to part of heart –ischaemic heart disease.
Preceded by coronary insufficiency syndrome.
Heart and Stroke Foundation
suggestions:
25% of myocardial infarcts MI have no chest pain
Paleness
Anxiety, fear, denial
Sweating
Shortness of breath
Indigestion
Tightness or chest pain
Overall weakness
Nausea PASS IT ON
Coronary artery disease
49 year old man, chest pain
during an argument.
Could it be MI?
Emergency Room, ECG done
Plasma CK/troponin I or T at time in ER,
then 6 and 12 hours after estimated time of
infarct
Plasma CKMB, (CK2)/troponin
Recently: serum or plasma myoglobin,
[glycogen phosphorylase BB].
troponin
Treatment of MI/Acute coronary
syndrome (ACS):
Aspirin – most patients self medicate before
ER.
Heparin
Tissue plasminogen activator
Platelet blockers – glycoprotein IIb/IIIa
($800-1,200)
Management post MI:
s-CK or s-troponin is followed over time. s-
CK is normal in a few days but s-troponin is
up for weeks.
Check for reperfusion
Check for reinfarction
Try to get life style changes in patient.
Markers for myocardial infarct
Critique of cardiac markers
Cardiac markers over time
Cardiac bypass surgery:
Heart stopped and by pass vein grafted round
obstruction
Brain is oxygenated but the rest of the body is not
(<4 hours)
Laboratory supplies blood gases and electrolytes
with 2 minute turn around time in laboratory.
“healthy” patients <1% die
“high risk” 25% die.
Need practice to do well – institute for clinical
evaluative studies ICES.
Cardiac by pass surgery:
Most common surgery in North America.
Up to 6/day at Sunnybrook.

Quality of life improved.

Death rate unchanged.
Some brain damage is common.
Congestive heart failure is a big
problems
Congestive heart failure:
Increased venous pressure, breathless, cough,
wheeze, oedema, hepatomegaly, raised jugular
venous pressure JVP, dizziness, syncope, fatigue,
low blood pressure, cardiomegaly.

Liver function tests, Natriuretic peptides A, B and

C type, Complete blood count CBC, Thyroid
function tests.
Cardiac changes leading to CHF
Ventricular Remodeling in post-AMI and in Heart Failure

NEJM (2003) 348:2007-18.

Natriuretic peptide
Pharmacologic Actions of BNP

Hemodynamic
(balanced vasodilation)
 venous tone

 arterial tone

R I SS
D S
M S
K
R
G
G
L Neurohumoral
G H
 renin/aldosterone release
F R
C S S CK V L R
G
S PKM V Q GS

Renal
diuresis
 natriuresis
Natriuretic peptide
Vasodilation
Promotion of natriuresis and diuresis
Inhibition of the sympathetic nervous
system
Inhibition of several hormone systems such
as the renin angiotensin aldosterone system
Effects on cardiovascular system
bnp
Production of BNP
Characteristics of the BNPs
BNP NT-proBNP
Hormonally active Hormonally inactive
22 minute half life 1-2 hours half life
Clearance through Clearance through the
natriuretic peptide
receptor C and reticuloendothelial
enzymatic degradation system and renal
by neutral clearance.
endopeptidase
Clinical use of BNP and NT-
proBNP
Diagnosis of heart failure (May be hard to
tell from COPD – SOB patients)
Prognostic marker for subsequent cardiac
events
Treatment monitoring for management of
heart failure patients.
BNP is not specific for CHF
Increased
post MI
Multiple trauma
Abdominal or thoracic surgery
Subarachnoid hemorrhage, some brain tumours
Diabetes
Renal failure
Pulmonary embolism, lung cancer
Ventricular hypertrophy and cardiomegaly
CHF BNP algorithm